DESCRIPTION: Oligodendrocyte-specific protein (OSP) is a recently isolated CNS myelin-specific protein, whose function and regulated expression during CNS development and glial tumorigenesis the applicant proposes to address. OSP's developmental expression in the brain will be characterized using in situ hybridization, to determine at which stage in oligodendrocyte differentiation the protein is likely to act. The promoter region of the OSP gene will be isolated and characterized in order to identify factors that regulate the cell-specific expression of this gene. This analysis will be performed in cell culture and in transgenic mice. Several lines of evidence support a role of OSP in regulating oligodendrocyte proliferation. Therefore, the effect of OSP gene dosage on oligodendroglial growth and myelination will be examined. Oligodendrocyte precursors will be transfected with a retroviral expression vector containing the OSP cDNA and OSP anti-sense cDNAs in order to determine the effect of over and under expression of OSP on cell growth and differentiation. Transgenic mice will be created with an OSP transgene driven by the myelin basic protein promoter to promote OSP overexpression, and OSP "knock-out" mice will be created to determine the effect of OSP underexpression. These mutant mice will be analyzed by immunohistochemistry, in situ hybridization, and electron microscopy, to reveal the morphological, structural, and biochemical effects of alterred OSP gene dosage. The applicant and his colleagues will also identify the proteins with which OSP interacts by exploiting the yeast two-hybrid system. Finally, they will examine expression of OSP and the copy number of the OSP gene in a number oligodendrogliomas, in an attempt to investigate its potential role in tumorigenesis.